Feasibility and Outcome of PSMA-PET-Based Dose-Escalated Salvage Radiotherapy Versus Conventional Salvage Radiotherapy for Patients With Recurrent Prostate Cancer

Abstract

IntroductionProstate-specific membrane antigen-positron emission tomography-(PSMA-PET) imaging facilitates dose-escalated salvage radiotherapy (DE-SRT) with simultaneous-integrated boost (SIB) for PET-positive lesions in patients with prostate cancer (PC). Therefore, we aimed to compare toxicity rates of DE-SRT with SIB to conventional SRT (C-SRT) without SIB and to report outcome.Materials and MethodsWe evaluated 199 patients who were treated with SRT between June 2014 and June 2020. 101 patients received DE-SRT with SIB for PET-positive local recurrence and/or PET-positive lymph nodes. 98 patients were treated with C-SRT to the prostate bed +/− elective pelvic lymphatic pathways without SIB. All patients received PSMA-PET imaging prior to DE-SRT ([68Ga]PSMA-11: 45.5%; [18F]-labeled PSMA: 54.5%). Toxicity rates for early (<6 months) and late (>6 months) gastrointestinal (GI) toxicities rectal bleeding, proctitis, stool incontinence, and genitourinary (GU) toxicities hematuria, cystitis, urine incontinence, urinary obstruction, and erectile dysfunction were assessed. Further, we analyzed the outcome with disease-free survival (DFS) and prostate-specific antigen (PSA) response.ResultsThe overall toxicity rates for early GI (C-SRT: 2.1%, DE-SRT: 1.0%) and late GI (C-SRT: 1.4%, DE-SRT: 5.3%) toxicities ≥ grade 2 were similar. Early GU (C-SRT: 2.1%, DE-SRT: 3.0%) and late GU (C-SRT: 11.0%, DE-SRT: 14.7%) toxicities ≥ grade 2 were comparable, as well. Early and late toxicity rates did not differ significantly between DE-SRT versus C-SRT in all subcategories (p>0.05). PSA response (PSA ≤0.2 ng/ml) in the overall group of patients with DE-SRT was 75.0% and 86.4% at first and last follow-up, respectively.ConclusionDE-SRT showed no significantly increased toxicity rates compared with C-SRT and thus is feasible. The outcome of DE-SRT showed good results. Therefore, DE-SRT with a PSMA-PET-based SIB can be considered for the personalized treatment in patients with recurrent PC.

Impact of 18F-Fluciclovine PET/CT Findings on Failure-Free Survival in Biochemical Recurrence of Prostate Cancer Following Salvage Radiation Therapy

“…One such role is radiation boost to imaging-identified positive lesions. This approach allows for the delivery of high radiation doses to the recurrent lesions without increasing the dose to normal tissues 29–31 . In view of this improved dose delivery to PCa recurrence lesions without increasing normal tissue toxicity from molecular imaging-guided radiotherapy boosting, patients in another ongoing trial (NCT03762759) receive a total of 64.8 to 70.2 Gy at 1.8 Gy per fraction to the prostate bed with a boost to 70.2 to 76.0 Gy to areas of radiotracer uptake on PET/CT imaging.…”

“…This approach allows for the delivery of high radiation doses to the recurrent lesions without increasing the dose to normal tissues. [29][30][31] In view of this improved dose delivery to PCa recurrence lesions without increasing normal tissue toxicity from molecular imaging-guided radiotherapy boosting, patients in another ongoing trial (NCT03762759) receive a total of 64.8 to 70.2 Gy at 1.8 Gy per fraction to the prostate bed with a boost to 70.2 to 76.0 Gy to areas of radiotracer uptake on PET/CT imaging. The results of this trial, when concluded, will advance knowledge regarding the comparative impact of these 2 imaging modalities on FFS post-SRT in men who are diagnosed with PCa recurrence post-RP.…”

ESTRO ACROP consensus recommendation on the target volume definition for radiation therapy of macroscopic prostate cancer recurrences after radical prostatectomy

“…In fact, a recent search on https://www.clinicatrials.gov only identified NCT05328505 and NCT01411345. At the moment, the clinical experience is also limited and mostly retrospective [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] . A similar approach was used in the recent phase 2, dual-center, open-label, single-arm SCIMITAR trial, testing extreme hypofractionation in patients with biochemical and/or clinical relapse [45] .…”

Can PSMA PET/CT help in dose-tailoring in post-prostatectomy radiotherapy?

“…Vogel et al. ( 20 ) used a simultaneous-integrated boost for PSMA-PET-positive lesions to 76.5 Gy in 2.25 Gy vs. 68 Gy in 2 Gy fractions. They found a better PSA-response rate for patients treated with dose-escalation.…”